Lipid Metabolism PDF Finals 2

28/04/2024 Lipids Digesti...

28/04/2024 Lipids Digestion and absorption of lipids Triacylglycerol storage and mobilization Glycerol Metabolism LIPID Oxidation of Fatty Acids ATP Production from Fatty Acid Oxidation METABOLISM TOPIC OUTLINE Ketone Bodies and Ketogenesis Biosynthesis of Fatty Acids: Lipogenesis Relationships between Lipogenesis and Citric Acid Cycle Intermediates Fate of Fatty-Acid-Generated Acetyl CoA Relationships Between Lipid and Carbohydrate Metabolism LIPID METABOLISM 4/28/2024 1 2 LIPIDS  The digestion of lipids starts in the mouth with lingual lipases, continues in the  A lipid is an organic DIGESTION AND stomach aided by lingual and compound found in living ABSORPTION OF gastric enzymes, and progresses significantly in the organisms that is insoluble LIPIDS duodenum where bile and (or only sparingly soluble) pancreatic juice play crucial in water but soluble in roles. nonpolar organic solutions. 4/28/2024 LIPID METABOLISM 4/28/2024 3 4  28/04/2024 MOUTH TO THE STOMACH IN THE STOMACH  Digestion of lipids starts in the mouth  In the stomach, gastric lipase breaks with saliva breaking them down. down triacylglycerols into diglycerides and Chewing and emulsifiers help enzymes fatty acids. About 30% of triacylglycerols start digestion, with lingual lipase and change into diglycerides and fatty acids some phospholipid beginning the within a few hours after eating. Stomach process and making fats easier for churning spreads fat molecules, and enzymes to act on, resulting in fats diglycerides help by acting as emulsifiers. forming small droplets separate from However, only a small amount of fat water. digestion happens in the stomach despite these actions. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 5 6 IN THE STOMACH TRAVELLING IN THE BODY  Inside intestinal cells, monoglycerides and fatty  Bile is vital for digesting and absorbing fats. acids come together to reform triacylglycerols. It mixes fats with watery fluids in the small These triacylglycerols, along with cholesterol intestine, using bile salts, lecithin, and and phospholipids, then combine with a protein cholesterol-based substances to increase carrier to create lipoproteins. These the surface area of fats for easier digestion lipoproteins, like chylomicrons, serve as by enzymes like pancreatic lipase. This transport vehicles, moving fats through both the breakdown produces free fatty acids and lymphatic system and bloodstream to various monoglycerides, aiding digestion further. tissues in the body. Additionally, consuming high-fiber foods can be Bile also helps fats pass through the beneficial for reducing cholesterol absorption. mucous layer, allowing absorption into This is because the fiber in these foods can bind digestive tract cells.These functions are to bile salts and cholesterol, aiding in their crucial for efficient digestion and nutrient elimination from the body and contributing to absorption in the body. lower cholesterol levels overall. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 7 8  28/04/2024 FAT ABSORPTION AND STORAGE  Fatty acids are stored primarily in adipocytes as triacylglycerol.Triacylglycerol must be hydrolyzed to  Carbohydrates not immediately used are release the fatty acids. stored as glycogen in muscles and then as  Adipocytes are found mostly in the abdominal cavity and triacylglycerols in the liver. Chylomicrons subcutaneous tissue. carry triacylglycerols to fat storage areas TRIACYLGLYCEROL  Adipocytes are metabolically very active; their stored like adipose tissue, where they're stored. triacylglycerol is constantly hydrolyzed and resynthesized. STORAGE AND Lipoprotein-lipase breaks down chylomicron triacylglycerols, allowing fatty acids and MOBILIZATION glycerol to enter adipose cells for storage. Adipose tissue releases stored triacylglycerols as needed for energy, with fatty acids and glycerol entering the bloodstream for cellular energy production. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 9 10 TRIACYLGLYCEROL STORAGE AND MOBILIZATION  Non-esterified fatty acid release from the adipocytes is initiated by the action of hormone sensitive lipase (HSL), which begins to hydrolyze the stored triglyceride.  The final products of triacylglycerol hydrolysis are glycerol and non- esterified fatty acids.  HSL is activated by epinephrine, norepinephrine,ACTH and glucagon, acting via phosphorylation of the enzyme.  It is inhibited by insulin.  Glycerol metabolism refers to the biochemical  Non-esterified fatty acids are bound to serum albumin for transport to other tissues, where they are used. processes involved in the breakdown and utilization of GLYCEROL glycerol, a three-carbon alcohol. Glycerol can be  Major target tissues are muscle and liver.  At the target cells non-esterified fatty acids are taken up passively. METABOLISM derived from various sources, such as triglycerides in Within the target cells they are bound to fatty acid binding protein. dietary fats, adipose tissue lipolysis, or glycerol- Next, they must be activated. containing compounds. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 11 12  28/04/2024 Glycerol Kinase: In some organisms, glycerol is phosphorylated by glycerol kinase GLYCEROL 1. to form glycerol-3-phosphate (G3P). This reaction occurs primarily in the liver and OXIDATION OF adipose tissue. METABOLISM 2. Glycerol-3-Phosphate Dehydrogenase: G3P is then converted to FATTY ACIDS dihydroxyacetone phosphate (DHAP) by glycerol-3-phosphate dehydrogenase. DHAP is an intermediate in both glycolysis and gluconeogenesis pathways. 3. Glycerol Utilization in Energy Production: In glycolysis, DHAP can be converted to glyceraldehyde-3-phosphate (GAP) to enter the energy-yielding steps of glycolysis. This process generates ATP and NADH, providing energy for cellular  Fatty acid oxidation is the functions. mitochondrial aerobic process of 4. Glyceroneogenesis: Glycerol can also contribute to glucose synthesis through a breaking down a fatty acid into process called glyceroneogenesis. In this pathway, DHAP produced from glycerol is acetyl-CoA units. Fatty acids converted to glucose-6-phosphate, which can then enter gluconeogenesis to produce move in this pathway as CoA glucose. derivatives utilizing NAD and 5. Triglyceride Synthesis: Glycerol is a crucial component in the synthesis of FAD. Fatty acids are activated triglycerides. It combines with fatty acids through esterification to form triglycerides, which are stored in adipose tissue for energy storage. before oxidation, utilizing ATP in 6. Regulation: Glycerol metabolism is tightly regulated to maintain energy balance the presence of CoA-SH and and glucose homeostasis. Hormones like insulin, glucagon, and adrenaline play key roles acyl-CoA synthetase. in regulating glycerol metabolism, influencing processes such as lipolysis and glycerol release from adipose tissue. LIPID METABOLISM 4/28/2024 4/28/2024 13 14 OXIDATION OF FATTY ACIDS: ACTIVATION OXIDATION OF FATTY ACIDS: TRANSPORT  Fatty acids are activated by fatty acyl CoA synthetase.  The reaction:  The fatty acyl group is transported into the mitochondrial matrix,  R-COOH + CoASH + ATP R-CO-SCoA + AMP + PPi where it undergoes beta-oxidation.  The subsequent hydrolysis of PPi draws the reaction in the forward direction, maintaining a low cytosolic free  In the intermembrane space of the mitochondria, fatty acyl CoA fatty acid concentration: reacts with carnitine in a reaction catalyzed by carnitine acyltransferase I (CAT-I), yielding CoA and fatty acyl carnitine. The  PPi + H2O --> 2 Pi resulting fatty acyl carnitine crosses the inner mitochondrial  The reaction occurs in the endoplasmic reticulum and the outer mitochondrial membrane. membrane. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 15 16  28/04/2024 ATP PRODUCTION FROM FATTY ACID OXIDATION 1. Fatty Acid Activation: Before fatty acids can enter the mitochondria for oxidation, ATP they undergo activation in the cytoplasm. This process requires ATP and coenzyme A (CoA) and converts the fatty acid into a fatty acyl-CoA molecule. PRODUCTION 2. Transport into Mitochondria: The fatty acyl-CoA molecule is then transported into the mitochondria with the help of a transport protein called carnitine. This step occurs in the outer mitochondrial membrane. FROM FATTY 3. Beta-Oxidation: Once inside the mitochondria, the fatty acyl-CoA undergoes beta- oxidation, which involves a series of enzymatic reactions: ACID  Step 1: Oxidation - The fatty acyl-CoA is oxidized by the enzyme acyl-CoA dehydrogenase, producing FADH2 (flavin adenine dinucleotide) and a trans-2-enoyl-  Fatty acid oxidation, also known as beta-oxidation, is OXIDATION a process that occurs in the mitochondria of cells and  CoA molecule. Step 2: Hydration - The trans-2-enoyl-CoA molecule undergoes hydration, catalyzed by enoyl-CoA hydratase, to form a 3-hydroxyacyl-CoA molecule. is responsible for breaking down fatty acids to  Step 3: Oxidation - The 3-hydroxyacyl-CoA molecule is oxidized again by beta- hydroxyacyl-CoA dehydrogenase, producing NADH and a 3-ketoacyl-CoA molecule. generate ATP (adenosine triphosphate), the energy  Step 4: Thiolytic Cleavage - The 3-ketoacyl-CoA molecule is cleaved by thiolase, currency of the cell. resulting in a new acetyl-CoA molecule and a shortened fatty acyl-CoA chain, which re-enters the beta-oxidation cycle until fully oxidized. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 17 18 ATP PRODUCTION FROM FATTY ACID OXIDATION KETONE BODIES AND KETOGENESIS 4. Acetyl-CoA Production: The acetyl-CoA molecules generated from beta-oxidation enter the citric acid cycle (also known as the Krebs cycle)  Ketone bodies are molecules produced in the liver from in the mitochondria, where they undergo further oxidation to produce fatty acids when glucose levels are low, such as during NADH, FADH2, and GTP (which can be converted to ATP). fasting or a low-carbohydrate diet. The three main 5. Electron Transport Chain (ETC): The NADH and FADH2 produced ketone bodies are acetone, acetoacetate, and beta- from both beta-oxidation and the citric acid cycle donate their electrons hydroxybutyrate. to the electron transport chain located in the inner mitochondrial  Ketogenesis is the process by which ketone bodies are membrane. This transfer of electrons generates a proton gradient across synthesized in the liver. It begins with the breakdown of the membrane. fatty acids into acetyl-CoA molecules through beta- 6. ATP Synthesis: The proton gradient created by the electron transport oxidation. These acetyl-CoA molecules can then enter chain drives ATP synthesis through ATP synthase. Protons flow back into the ketogenic pathway, where they are converted into the mitochondrial matrix through ATP synthase, and this flow of protons ketone bodies. powers the conversion of ADP (adenosine diphosphate) to ATP. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 19 20  28/04/2024 KETOGENESIS 1. Fatty Acid Breakdown: Triglycerides stored in adipose tissue are broken down into fatty acids and glycerol. Fatty acids are transported to the liver. 2. Beta-Oxidation: Within liver mitochondria, fatty acids undergo beta-oxidation, a series of reactions that break down fatty acids into acetyl-CoA molecules. This process generates NADH and FADH₂, which enter the electron transport chain for BIOSYNTHESIS OF ATP production. 3. Acetyl-CoA Formation: Acetyl-CoA is the product of beta-oxidation and is a key FATTY ACIDS: molecule in ketogenesis. LIPOGENESIS 4. Ketogenesis Steps: Acetyl-CoA molecules are condensed to form acetoacetyl-CoA, which is then converted to hydroxymethylglutaryl-CoA (HMG-CoA). HMG-CoA is then cleaved to yield acetoacetate, the first ketone body.  Lipogenesis refers to the biological process through which the body 5. Ketone Body Conversion: Acetoacetate can be converted to acetone or reduced to synthesizes or creates fats. It involves the conversion of carbohydrates beta-hydroxybutyrate (BHB). Acetone is a volatile ketone that is exhaled, while BHB is the main circulating ketone body. or other substrates into fatty acids and ultimately into triglycerides, which are stored in adipose tissue as a form of energy reserve. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 21 22 LIPOGENESIS 1. Glucose Uptake: Glucose from carbohydrates is taken up by cells, especially in the liver and fat tissue. RELATIONSHIPS 2. Conversion to Acetyl-CoA: Glucose undergoes glycolysis BETWEEN to produce pyruvate, which is then converted to acetyl-CoA. 3. Acetyl-CoA Carboxylation: Acetyl-CoA is converted to LIPOGENESIS AND malonyl-CoA through carboxylation, which is a key regulatory step. CITRIC ACID  The relationship between lipogenesis and 4. Fatty Acid Synthesis: In the cytoplasm, fatty acids are CYCLE the citric acid cycle (also known as the synthesized from malonyl-CoA and acetyl-CoA through a series of enzymatic reactions called fatty acid synthesis. INTERMEDIATES Krebs cycle or tricarboxylic acid cycle) 5. Formation of Triglycerides: The fatty acids produced are then combined with glycerol to form triglycerides. intermediates lies in the metabolic pathways 6. Storage in Adipose Tissue: The newly formed triglycerides involved in energy production and storage are packaged into lipoprotein particles and stored in adipose tissue as a long-term energy reserve. in cells. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 23 24  28/04/2024 RELATIONSHIPS BETWEEN LIPOGENESIS AND CITRIC ACID CYCLE INTERMEDIATES  Acetyl-CoA can be derived by the breakdown of 1. Acetyl-CoA: This is a central molecule that connects both lipogenesis and the citric acid cycle. Acetyl-CoA glucose, fatty acids, proteins or amino acids, and is a product of fatty acid oxidation, and it enters the citric acid cycle to generate energy through the production of NADH and FADH2. Additionally, acetyl-CoA is a precursor for fatty acid synthesis during alcohol. lipogenesis.The balance between using acetyl-CoA for energy production or for fatty acid synthesis depends on the metabolic state of the cell.  Acetyl-CoA generated from fatty acids has 2. Citrate: In the citric acid cycle, citrate is formed when acetyl-CoA combines with oxaloacetate. Citrate can several potential fates within the cell, depending exit the mitochondria and serve as a substrate for fatty acid synthesis in the cytoplasm. This process, known FATE OF FATTY- as citrate shuttle or citrate transport, provides a means for transporting acetyl-CoA units from the on the metabolic needs and conditions. Here are mitochondria (where they are generated during the breakdown of glucose or fatty acids) to the cytoplasm for ACID- some of the primary pathways: fatty acid synthesis. GENERATED 3. Malonyl-CoA: This is an intermediate in fatty acid synthesis and acts as an inhibitor of carnitine palmitoyltransferase 1 (CPT-1), an enzyme involved in transporting fatty acids into the mitochondria for beta- ACETYL COA oxidation.When malonyl-CoA levels are high (indicating a need for fatty acid synthesis), CPT-1 is inhibited, reducing the breakdown of fatty acids for energy production. 4. Oxaloacetate: This is a key intermediate in the citric acid cycle, and its availability can influence the rate of the cycle. When cellular energy levels are high (e.g., during lipogenesis), oxaloacetate can be diverted from the citric acid cycle to participate in gluconeogenesis or fatty acid synthesis. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 25 26 FATE OF FATTY-ACID-GENERATED ACETYL COA 1. Energy Production (Citric Acid Cycle): Acetyl-CoA enters the citric acid cycle (also known as the Krebs cycle or tricarboxylic acid cycle) in the mitochondria. Here, it undergoes a series of enzymatic reactions, ultimately leading to the generation of ATP through oxidative phosphorylation. 2. Ketogenesis: Under certain conditions such as fasting or low carbohydrate intake, excess acetyl-CoA derived from RELATIONSHIPS fatty acids can be converted into ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) in the liver. These ketone bodies can then be used as alternative fuels by tissues like the brain and muscles. BETWEEN LIPID 3. Lipogenesis: Acetyl-CoA can also be used for de novo synthesis of fatty acids (lipogenesis). This occurs primarily AND  Lipid and carbohydrate metabolism are closely linked processes in the body, influencing each other's functions. Carbohydrates are the in the liver and adipose tissue when there is an excess of energy or during conditions like high-carbohydrate intake. CARBOHYDRATE main energy source, with excess glucose converted into lipids for 4. Cholesterol Synthesis: Acetyl-CoA is a precursor for the synthesis of cholesterol in the liver. This process is storage. Insulin regulates both processes, promoting glucose uptake important for the production of cell membranes, hormones, and bile acids. METABOLISM and lipogenesis. Glycogen and lipid stores provide energy reserves, 5. Acetylation Reactions: Acetyl-CoA serves as a substrate for acetylation reactions, where acetyl groups are while ketogenesis offers an alternative fuel source during low transferred to various molecules, including proteins, to regulate their functions. carbohydrate intake. Lipoprotein metabolism is influenced by dietary fats and carbohydrates, impacting cardiovascular health. Imbalances 6. Histone Acetylation: Acetyl-CoA is also involved in epigenetic regulation through histone acetylation, which can influence gene expression. in these pathways can lead to metabolic disorders like obesity and diabetes, emphasizing the importance of understanding and 7. Oxidative Stress Management: Acetyl-CoA can participate in the synthesis of antioxidants such as glutathione, managing lipid-carbohydrate interactions for overall metabolic well- helping to mitigate oxidative stress in cells. being. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 27 28  28/04/2024 RELATIONSHIPS BETWEEN LIPID AND CARBOHYDRATE METABOLISM 1. Energy Source: Carbohydrates are the primary energy source for the body, readily broken down into glucose. REFERENCES: Glucose is used for immediate energy needs or stored as glycogen in the liver and muscles. When energy demands exceed glycogen reserves, lipids (fats) are broken down into fatty acids and glycerol for energy production. 2. Insulin and Glucagon: Insulin, released by the pancreas, regulates glucose levels by promoting its uptake into cells for energy or storage. It also inhibits lipolysis (breakdown of fats). In contrast, glucagon, also from the pancreas, stimulates the breakdown of glycogen and fats to increase blood glucose levels when needed. 3. Lipogenesis and Lipolysis: Lipogenesis is the process of synthesizing lipids from excess glucose or other substrates.  https://med.libretexts.org/ This occurs when there's an abundance of glucose, often seen after high-carbohydrate meals. Lipolysis, on the other hand, breaks down lipids into fatty acids and glycerol. It's triggered during fasting or when glucose levels are low, such as  https://library.med.utah.edu/ during prolonged exercise or fasting.  https://www.sciencedirect.com/ 4. Ketogenesis: When carbohydrates are limited, such as during a low-carb diet or fasting, the body increases the breakdown of fats into ketone bodies through ketogenesis. These ketone bodies can then be used as an alternative fuel  https://www.cambridge.org/ source, particularly by the brain and muscles.  Biochemistry 3rd Edition by H. Stephen Stoker 5. Role of Hormones: Besides insulin and glucagon, other hormones influence lipid and carbohydrate metabolism. For instance, cortisol (a stress hormone) can stimulate lipolysis and gluconeogenesis (production of glucose from non- carbohydrate sources) during periods of stress or fasting. 6. Metabolic Syndrome: Dysregulation in either lipid or carbohydrate metabolism can contribute to metabolic syndrome, a cluster of conditions like obesity, high blood pressure, high blood sugar, and abnormal lipid levels. This often involves insulin resistance, where cells become less responsive to insulin, leading to elevated blood sugar and lipid levels. LIPID METABOLISM 4/28/2024 LIPID METABOLISM 4/28/2024 29 30  05/05/2024 Protein Digestion and Absorption Amino Acid Utilization Transamination and Oxidative Deamination Prepared By: Veronica Baje The Urea Cycle Environmental Science Program College Of Arts And Sciences Amino Acid Carbon Skeletons Our Lady Of Fatima University San Fernando, Pampanga Amino Acid Biosynthesis Hemoglobin Catabolism Proteins and the Element Sulfur Interrelationships Among Metabolic Pathways 5/5/2024 Week 14 - Protein Metabolism 1 2 Protein digestion begins in the mouth with chewing and salivary enzymes, followed by Mouth: Mechanical breakdown of food occurs through stomach acid and enzymes breaking down chewing, and salivary enzymes like amylase begin breaking proteins into smaller peptides. In the small down carbohydrates. intestine, pancreatic enzymes further break Stomach: Proteins encounter the acidic environment of the down proteins into amino acids and stomach. Here, pepsinogen is converted to pepsin, which peptides, which are then absorbed into starts breaking down proteins into smaller peptides. enterocytes through specific transporters. Small Intestine: The partially digested food, called chyme, These amino acids enter the bloodstream moves into the small intestine. The pancreas releases via the portal vein and are utilized for pancreatic enzymes (trypsin, chymotrypsin, carboxypeptidase) to further break down proteins into protein synthesis, energy production, and peptides and amino acids. the synthesis of various molecules. Excess Intestinal Brush Border Enzymes: Peptides are broken amino acids are processed in the liver and down into amino acids or dipeptides and tripeptides by eliminated as urea via the kidneys. enzymes like peptidases on the brush border of the small intestine. 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 3 4  05/05/2024 Amino Acid Transporters: Amino acids are absorbed into the enterocytes (cells lining the small intestine) through specific Protein Synthesis: Amino acids are used to build new proteins essential amino acid transporters. for growth, repair, and maintenance of tissues. Peptide Transporters: Dipeptides and tripeptides are also Energy Production: Amino acids can be converted into glucose or absorbed via peptide transporters and then broken down into individual amino acids within the enterocytes. ketone bodies for energy when carbohydrates and fats are insufficient. Portal Circulation: Amino acids are transported across the Synthesis of Non-Protein Molecules: Amino acids are used to enterocyte and enter the bloodstream through the portal vein, synthesize various molecules like hormones, enzymes, and which carries them to the liver. neurotransmitters. Liver Processing: In the liver, amino acids may be used for protein synthesis, converted to energy, or undergo further Nitrogen Excretion: Excess amino acids are deaminated in the liver, metabolic processes. producing ammonia, which is converted to urea and excreted via the kidneys. 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 5 6 TRANSAMINATION – the transfer of an alpha-amino Ammonia is a toxic product of nitrogen group from an alpha-amino acid to an alpha-keto acid metabolism which should be removed via an aminotransferase. from our body. The urea cycle or The two most important aminotransferases are: ornithine cycle converts excess ammonia into urea in the mitochondria Aspartate aminotransferase (AST) of liver cells. The urea forms, then Alanine aminotransferase (ALT) enters the blood stream, is filtered by OXIDATIVE DEAMINATION – the release of ammonium the kidneys and is ultimately excreted in via a conversion of glutamate to alpha-ketoglutarate. the urine. 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 7 8  05/05/2024 1. Formation of Carbamoyl Phosphate: The cycle starts in the mitochondria of liver cells. Here, ammonia (NH3) and carbon dioxide (CO2) combine to form carbamoyl phosphate. This reaction is catalyzed by the enzyme carbamoyl phosphate synthetase I (CPS I), which requires ATP (adenosine triphosphate). Amino acid carbon skeletons are transformed into major metabolic 2. Formation of Citrulline: The carbamoyl phosphate then combines with ornithine to produce citrulline. intermediates that can be: This reaction takes place in the mitochondria and is catalyzed by the enzyme ornithine transcarbamylase (OTC). Oxidized via the TCA Cycle 3. Citrulline Transport: Citrulline is transported from the mitochondria to the cytosol of the liver cell. Converted to Glucose 4. Formation of Argininosuccinate: In the cytosol, citrulline reacts with aspartate to form argininosuccinate. This reaction is catalyzed by the enzyme argininosuccinate synthase. Key intermediates: 5. Formation of Arginine and Fumarate: Argininosuccinate is then cleaved into arginine and fumarate by the enzyme argininosuccinate lyase. Pyruvate: Comes from breaking down sugars for energy (like glucose). 6. Arginine to Urea and Ornithine: Arginine is hydrolyzed to form urea and regenerate ornithine. This Acetyl CoA: Made from pyruvate, it's a big player in making energy in the mitochondria. reaction is catalyzed by arginase. Acetoacetyl CoA: Helps make backup energy sources called ketone bodies. 7. Recycling of Ornithine: Ornithine produced in step 6 is transported back into the mitochondria to initiate another round of the urea cycle. Alpha-Ketoglutarate: Works in the energy-making cycle called the TCA cycle. Succinyl CoA: Also part of the TCA cycle, helps make energy molecules like ATP. 8. Excretion of Urea: Urea, the final product of the cycle, is released into the bloodstream and eventually excreted by the kidneys in the urine. Fumarate: Another part of the TCA cycle, linked to making sugar from scratch when needed. 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 9 10 2. Specific Pathways: Amino acid biosynthesis refers to the 2. Glycolysis and Gluconeogenesis: These pathways provide intermediates for amino acid biosynthesis. For example, pyruvate from glycolysis can be converted into alanine or serine. biochemical pathways through which organisms produce amino acids, the building 3. Krebs Cycle (Citric Acid Cycle): This cycle generates alpha-ketoglutarate, oxaloacetate, blocks of proteins. These pathways are crucial and other intermediates used in amino acid synthesis. for maintaining cellular functions, growth, and 4. Pentose Phosphate Pathway: Provides ribose-5-phosphate, which is essential for development. nucleotide synthesis, and erythrose-4-phosphate, used in the synthesis of aromatic amino acids. 1. Essential vs. Non-Essential Amino Acids: 5. Transamination: A common reaction where amino groups are transferred between Essential amino acids are those that the different amino acids, allowing for the synthesis of non-essential amino acids. body cannot synthesize on its own and 3. Regulation: must be obtained from the diet. There are 2. Amino acid biosynthesis is tightly regulated to maintain proper cellular balance and nine essential amino acids for humans. respond to metabolic demands. Non-essential amino acids are 3. Feedback inhibition, gene regulation, and allosteric regulation of enzymes are some synthesized within the body and do not mechanisms involved in controlling these pathways. need to be consumed in the diet. 4. Nutrient availability, energy status, and hormonal signals also influence the regulation of amino acid biosynthesis. 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 11 12  05/05/2024 1. Hemolysis: The first step in hemoglobin catabolism is the destruction of red blood cells, known as hemolysis. This can occur due to aging of red blood cells or in certain medical conditions. 2. Release of Hemoglobin: Once red blood cells are destroyed, hemoglobin is released into the bloodstream. Hemoglobin catabolism refers 3. Binding to Haptoglobin: Free hemoglobin binds to a plasma protein called haptoglobin. This binding serves to prevent the loss of hemoglobin through the kidneys and also protects tissues from the toxic effects of free to the breakdown of hemoglobin. hemoglobin, the protein 4. Transport to Macrophages: The haptoglobin-hemoglobin complex is taken up by macrophages, which are responsible for carrying specialized immune cells. Macrophages are particularly abundant in the spleen and liver, where much of the hemoglobin breakdown occurs. oxygen in red blood cells. This 5. Lysosomal Degradation: Within macrophages, the haptoglobin-hemoglobin complex is broken down in lysosomes. process occurs primarily in the Lysosomes contain enzymes that degrade proteins into smaller peptides and amino acids. spleen and liver and involves 6. Heme and Globin Breakdown: The heme portion of hemoglobin is further degraded into biliverdin, which is then converted into bilirubin. Bilirubin is released into the bloodstream and eventually excreted in bile. The globin portion several steps. of hemoglobin is broken down into amino acids, which can be reused by the body for protein synthesis. 7. Iron Recycling: Iron released during heme breakdown is either stored in ferritin for future use or transported by transferrin to the bone marrow for the production of new red blood cells. 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 13 14 1. Transsulfuration Pathway: 1. Step 1: Methionine is converted to homocysteine by removing a methyl group. 2. Step 2: Homocysteine then combines with serine to form cystathionine, catalyzed by the enzyme cystathionine β-synthase (CBS). Sulfur is a critical element in proteins, especially due to its presence in the sulfur- 3. Step 3: Cystathionine is cleaved into cysteine containing amino acids cysteine and methionine. Cysteine contributes to protein and α-ketobutyrate by the enzyme structure through its ability to form disulfide bonds, which help stabilize protein folding cystathionine γ-lyase (CGL). and shape. Methionine, on the other hand, plays a role in the initiation of protein 2. Cysteine Biosynthetic Pathway (Sulfate synthesis. assimilation pathway): 1. Step 1: Sulfate is activated to adenosine 5'- In proteins, sulfur's involvement in disulfide bonds is vital for maintaining the proper phosphosulfate (APS). three-dimensional structure of many proteins, influencing their stability and function. 2. Step 2: APS is reduced to sulfite by APS These bonds can create loops, stabilize protein domains, or link separate protein reductase. molecules together. Overall, sulfur's presence in proteins is essential for their structural 3. Step 3: Sulfite is reduced to sulfide by sulfite integrity and functionality. reductase. 4. Step 4: O-Acetylserine (OAS) combines with sulfide to form cysteine, catalyzed by O- acetylserine (thiol)-lyase (OASTL or OAS-TL). 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 15 16  05/05/2024 These pathways are interconnected and regulated by hormones, enzymes, and substrate availability to ensure Cysteine can be degraded through several pathways: a constant supply of energy and essential molecules for cellular functions. Here’s an explanation of how these metabolic pathways interact: 1. Cysteine Dioxygenase Pathway: 1. Step 1: Cysteine is oxidized by cysteine dioxygenase to form 1. Carbohydrate Metabolism: cysteine sulfinate. 1. Glycolysis: Glucose breaks down into pyruvate, creating energy in cells. 2. Step 2: Cysteine sulfinate is further metabolized to hypotaurine 2. Storage (Glycogenesis): Extra glucose gets stored as glycogen in the liver and muscles. and taurine. 3. Release (Glycogenolysis): When needed, glycogen breaks down to release glucose into the bloodstream. 2. Mercaptopyruvate Sulfurtransferase Pathway: 2. Lipid Metabolism: 1. Step 1: Cysteine is first converted to mercaptopyruvate by 1. Breakdown (Lipolysis): Stored fats break down into fatty acids and glycerol for energy. cysteine aminotransferase. 2. Energy Production (Beta-Oxidation): Fatty acids turn into energy units called acetyl-CoA. 2. Step 2: Mercaptopyruvate is then metabolized to pyruvate and 3. Alternative Fuel (Ketogenesis): Acetyl-CoA can also form ketone bodies during low carb intake. hydrogen sulfide by mercaptopyruvate sulfurtransferase. 3. Protein Metabolism: 3. Cysteine Desulfuration Pathway: 1. Breakdown (Proteolysis): Proteins break down into amino acids. 1. Step 1: Cysteine is converted to pyruvate and hydrogen sulfide by 2. Energy Usage: Amino acids can be used for energy or to build new proteins. cysteine desulfhydrase. 3. Nitrogen Removal (Transamination): Unused amino acids may undergo transamination to remove nitrogen. 5/5/2024 Week 14 - Protein Metabolism 5/5/2024 Week 14 - Protein Metabolism 17 18 1. Feasting: 1. Eat, Store, Use: When you eat a lot, your body https://byjus.com/biology/digestion-and-absorption/ stores extra energy as fat and sugar for later when you need it. https://ditki.com/course/biochemistry/glossary/biochemical-pathway/transamination- 2. Digest and Store: Food gets broken down, and the oxidative-deamination body saves what it doesn't need right away. 2. Fasting: https://www.news-medical.net/health/What-is-the-Urea- 1. Switch to Stored Energy: When you don't eat for a Cycle.aspx#:~:text=Ammonia%20is%20a%20toxic%20product,ultimately%20excreted while, your body switches to using stored energy, %20in%20the%20urine. first from sugar, then from fat. 2. Use What's Saved: Your body taps into the energy https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00825/ it stored before when you were eating. full 3. Starvation: 1. Slow Down, Use Less: If you go without food for a long time, your body slows down to save energy, using less of what it saved up. 2. Emergency Mode: It starts using up muscles and 5/5/2024 Week 14 - Protein Metabolism fat because there's not enough food coming in. 5/5/2024 Week 14 - Protein Metabolism 19 20  12/05/2024 Topic Outline Nutrition Macronutrients vs Micronutrients Water and Fiber Carbohydrates NUTRITION Lipids PREPARED BY: VERONICA BAJE ENVIRONMENTAL SCIENCE PROGRAM Proteins COLLEGE OF ARTS AND SCIENCES OUR LADY OF FATIMA UNIVERSITY Vitamins SAN FERNANDO, PAMPANGA Micronutrients I Micronutrients II Water-soluble vitamins Fat-soluble vitamins Major and Trace Mineral Sources and Functions 5/ 12/ 2024 WE EK 15 - NU TRITION 1 2 Nutrition Nutrition is the study of food and how it affects the health and growth of the Macronutrients vs body. Nutrients are substances found in foods Micronutrients that our bodies use to grow, reproduce Macronutrients – are needed in and survive. large amounts (gram/s) as they There are 5 major nutrients we get from provide energy and materials food: required to build and repair Macronutrients: tissues 1. Carbohydrates Carbohydrates, protein, and 2. Proteins lipids 3. Lipids Micronutrients – required in small Micronutrients amounts (milligram or microgram) 4. Vitamins and many are used in enzymes. 5. Minerals Vitamins and minerals 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 3 4  12/05/2024 Water and Fiber In addition to nutrients, the body also Nutrition Daily requires water and fiber: Values Water – 45% to 75% of human body mass is water. Water also keep the The Daily Values (DV) are bloodstream liquid enough to flow reference amounts through blood vessels. Help (expressed in grams, eliminate the by-products of the body's metabolism, excess milligrams, or micrograms) of electrolytes (for example, sodium and nutrients to consume or not potassium), and urea. to exceed each day. Fiber – is an indigestible plant material made mostly of cellulose. It helps maintain digestive health by providing roughage to stimulate contraction of the intestines. 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 5 6 Nutrition Daily Carbohydrates Values cont’d: Carbohydrates provide energy for body The Food and Drug Authority functions and useful materials for the (FDA) has set nutritional synthesis of cell and tissue components. guidelines to be used on food Simple carbohydrates: labels. monosaccharides and disaccharides (glucose, fructose, sucrose etc.). Complex carbohydrates: polysaccharides amylose and amylopectin (starch). Current recommendations are that about 58% of our daily calories should come from carbohydrates. 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 7 8  12/05/2024 Lipids Lipids cont’d About 95% of the lipids in foods and in Lipids improve the our bodies is in the form of triglycerides. The fatty acids in the triglycerides can be texture of foods, absorb either saturated or unsaturated. and retain flavors, and Oils – triglycerides containing a high are digested more slowly concentration of unsaturated fatty acids are liquids at room temperature. than other foods, Fats – triglycerides containing a high prolong the feeling of concentration of saturated fatty acids are solids at room temperature. satiety (satisfaction and Lipids contain some fat-soluble vitamins fullness after a meal). and help to carry them through the body. 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 9 10 Micronutrients I: Proteins Vitamins Proteins is necessary for production Vitamins are organic of new tissue, maintenance and micronutrients that the body repair of cells, and production of cannot produce in amounts enzymes, hormones, and other important nitrogen-containing needed for good health. compounds. Some vitamins are highly polar During digestion, proteins are and are water-soluble. broken down into amino acids, Excess amounts of water- which are then absorbed into the soluble vitamins are usually body’s amino acid pool. removed by the kidneys. 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 11 12  12/05/2024 Fat-Soluble and Water- Soluble Vitamins Fat-soluble vitamins are stored in the body's liver, fatty tissue, and muscles. These vitamins are absorbed more easily by the body in the presence of dietary fat. Vitamins A, D, E, and K VITAMIN Water-soluble vitamins are not stored in the CHEAT body. Any leftover or excess amounts of these leave the body through the urine. They have to be SHEET consumed on a regular basis to prevent shortages or deficiencies in the body. The exception to this is vitamin B12, which can be stored in the liver for many years. Vitamin C and all the B Vitamins except B12 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 13 14 Micronutrients II: Trace Minerals Minerals Minerals are metals or non-metals used in Trace elements (or trace metals) the body in the form of ions or are minerals present in living compounds. tissues in small amounts. Some Minerals are those elements on the earth of them are known to be and in foods that our bodies need to nutritionally essential, others develop and function normally. Those may be essential (although the essential for health include calcium, phosphorus, potassium, sodium, chloride, evidence is only suggestive or magnesium, iron, zinc, iodine, chromium, incomplete), and the remainder copper, fluoride, molybdenum, are considered to be manganese, and selenium. nonessential. 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 15 16  12/05/2024 Major and Trace References: Minerals https://medlineplus.gov/ency/article/002399 https://cheatdaydesign.com/vitamin-cheat-sheet/ https://byjus.com/biology/micronutrients/ https://www.ncbi.nlm.nih.gov/books/NBK218751/ 5/ 12/ 2024 WE EK 15 - N UTRITION 5/ 12/ 2024 WE EK 15 - NU TRITION 17 18  21/05/2024  Body Fluid Balance  Intracellular and  Regulation of Fluid Extracellular Fluids Balance  Chemical Composition of  Acid Base Balance BODY  Blood Body Fluids  Buffer Control of Blood pH FLUIDS  Constituents of Blood  Respiratory Control of  Functions of Blood Blood pH  Blood Types  Urinary Control of  Hemoglobin Blood pH Prepared by: Veronica Baje  Oxygen Binding  Acidosis and Alkalosis Environmental Science Department  Carbon Dioxide Binding College of Arts and Sciences  Respiratory Alkalosis and Our Lady of Fatima University  Flow Between Blood And San Fernando, Pampanga Acidosis Interstitial Fluid  Metabolic Alkalosis and  Urine Topic Outline  Abnormal Urine Acidosis  Causes of Acid Base Constituents Imbalances  Fluid and Electrolyte 21/05/2024 Week 16 & 17 - Body Fluids 1 2 Intracellular fluid (ICF) I. Body Fluid Intracellular fluid (ICF) or cytosol accounts for two-thirds of all body fluid Body fluids are aqueous liquids and is found within cells, separated into containing the cellular and compartments by various organelle membranes. ionic components necessary for proper body function while Ionic concentrations (such as sodium and potassium) are critical to proper also providing transport for a ICF function, as it is the difference vast array of solutes and between these levels and ion concentrations found outside the cell products of metabolism. Body that drive several essential cellular fluids can be most generally processes, including: categorized according to Osmoregulation whether they reside inside the Cell signaling Creation of action potentials in cell membrane or surrounding endocrine, muscle and nerve cells it. 21/05/2024 Week 16 & 17 - Body Fluids 21/05/2024 Week 16 & 17 - Body Fluids 3 4  21/05/2024 Extracellular fluid Chemical Composition of Body Fluids (ECF) Extracellular fluid (ECF) accounts for about one-third of the body’s total fluid content, immersing cells and providing a medium for the movement of nutrients and metabolic waste products throughout the body. Body Fluids Composition ECF can be sub-categorized according to composition, function and body location, and includes: Intracellular Body Fluids 70% water, ions, and molecules Plasma Lymph Extracellular Body Fluids Cations and anions Cerebrospinal fluid (CSF) Saliva Transcellular Fluid Electrolytes such as sodium, bicarbonate, Interstitial fluid and chloride ions. Other body-generated fluids such as milk, sweat and urine 21/05/2024 Week 16 & 17 - Body Fluids 5/21/2024 Week 16 & 17 - Body Fluids 5 6 Constituents of II. Blood Blood Plasma constitutes 55% of Blood is a specialized body fluid. It has four blood fluid while the remaining main components: plasma, red blood cells, 45% are made up of blood cells. white blood cells, and platelets. Blood has